Reciprocally Retained Genes in the Angiosperm Lineage Show the Hallmarks of Dosage Balance Sensitivity

Abstract

In several organisms, particular functional categories of genes, such as regulatory and complex-forming genes, are preferentially retained after whole-genome multiplications but rarely duplicate through small-scale duplication, a pattern referred to as reciprocal retention. This peculiar duplication behavior is hypothesized to stem from constraints on the dosage balance between the genes concerned and their interaction context. However, the evidence for a relationship between reciprocal retention and dosage balance sensitivity remains fragmentary. Here, we identified which gene families are most strongly reciprocally retained in the angiosperm lineage and studied their functional and evolutionary characteristics. Reciprocally retained gene families exhibit stronger sequence divergence constraints and lower rates of functional and expression divergence than other gene families, suggesting that dosage balance sensitivity is a general characteristic of reciprocally retained genes. Gene families functioning in regulatory and signaling processes are much more strongly represented at the top of the reciprocal retention ranking than those functioning in multiprotein complexes, suggesting that regulatory imbalances may lead to stronger fitness effects than classical stoichiometric protein complex imbalances. Finally, reciprocally retained duplicates are often subject to dosage balance constraints for prolonged evolutionary times, which may have repercussions for the ease with which genome multiplications can engender evolutionary innovation.

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“…We then tested 155 whether functionally related gene groups-gene ontologies (GO) or metabolic networks (Schlapfer et al 2017)-exhibited patterns of reciprocal retention. As previously observed (Freeling 2009;Coate et al 2016;Tasdighian et al 2017), we found that both GO terms and metabolic networks with high retention following WGD tended to have lower retention of SSD (linear regression for GO terms, slope = −0.6972, R 2 = 0.1839, F = 175.05 , df = 1 and 777, P < 0.001; linear regression for metabolic networks, slope = 0.6667, R 2 = 0.0886, F = 17.31, df = 1 and 178, P < 0.001 ; Fig. 1 a,b).…”

“…Three main lines of evidence support the GBH (Tasdighian et al 2017;Freeling 2009;Hou et al 2018;Edger and Pires 2009): 1) signaling cascades, regulatory networks and protein complexes that are known to be disrupted by unbalanced changes in protein abundance tend to exhibit reciprocal 35 retention patterns; 2) reciprocally retained genes exhibit greater selective constraint on sequence evolution (lower Ka/Ks) and less divergence in expression patterns than non-reciprocally retained genes; and 3) reciprocally retained genes often exhibit deleterious phenotypes when over or under expressed-this latter piece of evidence often cited as the ultimate proof needed to demonstrate dosage sensitivity and confirm the GBH. However, demonstrating that a deleterious phenotype is 40 induced by over-or under-expressing a gene provides evidence for dosage sensitivity at the protein level, but it does not necessarily follow that there exists dosage sensitivity at the level of gene copy number.…”

“…Gene duplication is prevalent in eukaryotic genomes, occurring with a frequency similar to that of single nucleotide substitutions (Lynch andConery 2000, 2003;Tasdighian et al 2017), and is a major contributor to genetic diversity and the evolution of novel traits (Lynch and Conery 2000) Most gene duplicates, however, are eventually pseudogenized and/or deleted from the genome, with 5 an estimated half life for duplicated genes in plants of 17 MY (Lynch and Conery 2003). Following whole genome duplication (WGD, polyploidy) the majority of duplicated gene pairs (homoeologues) return to single copy (fractionate) in the process of diploidization (Langham et al 2004;Schnable et al 2011).…”

“…Certain classes of genes are preferentially retained in duplicated following WGD (Blanc and Wolfe 2004), and many of these same genes 15 exhibit minimal duplication via SSD (e.g., tandem duplication, transposition) (Freeling 2009). This pattern, in which some classes of genes preferentially retain duplicates originating from WGD but retain few duplicates derived from SSD is referred to as "reciprocal retention" (Tasdighian et al 2017). 20 Several models have been proposed to explain the long-term retention of duplicated genes (Panchy et al 2016) including the evolution of new functions (neofunctionalization), division of ancestral function (subfunctionalization), selection on absolute dosage, and the Gene Balance Hypothesis (GBH) (Freeling 2009;Birchler and Veitia 2012;Papp et al 2003).…”

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“…Overall, gene families evolve through gene duplication and loss events. Duplications can be divided into two overall categories: whole-genome multiplications (WGM) and small-scale duplications (SSD), including segmental, tandem, and transposoninduced duplication events (Panchy et al, 2016;Tasdighian et al, 2017). Individual gene families evolve by either one of these processes.…”